rs999842

Positions:

• chr15-22872796-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014608.6(CYFIP1):​c.3597+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,608,006 control chromosomes in the GnomAD database, including 249,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20599 hom., cov: 32)
  • Exomes 𝑓: 0.56 (229011 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

CYFIP1 (HGNC:13759): (cytoplasmic FMR1 interacting protein 1) This gene encodes a protein that regulates cytoskeletal dynamics and protein translation. The encoded protein is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. This protein also interacts with the synaptic functional regulator FMR1 protein and translation initiation factor 4E to inhibit protein translation. A large chromosomal deletion including this gene is associated with increased risk of schizophrenia and epilepsy in human patients. Reduced expression of this gene has been observed in various human cancers and the encoded protein may inhibit tumor invasion. [provided by RefSeq, Mar 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.3597+29A>G		intron_variant		ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.3597+29A>G		intron_variant		1	NM_014608.6	ENSP00000481038	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78099 AN: 151868 Hom.: 20598 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.490

GnomAD3 exomes AF: 0.552 AC: 138260 AN: 250408 Hom.: 39069 AF XY: 0.555 AC XY: 75153 AN XY: 135368

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.572

Gnomad FIN exome AF: 0.662

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.558 AC: 812410 AN: 1456020 Hom.: 229011 Cov.: 31 AF XY: 0.558 AC XY: 404613 AN XY: 724568

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.514 AC: 78129 AN: 151986 Hom.: 20599 Cov.: 32 AF XY: 0.519 AC XY: 38537 AN XY: 74298

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.488

Alfa AF: 0.538 Hom.: 15585

Bravo AF: 0.499

Asia WGS AF: 0.536 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs999842; hg19: chr15-23000272;